Color change of chalcone-containing oral care formulations

ABSTRACT

Oral care compositions and methods are described in which the composition includes a chalcone color change component, which may be phenyl-3-methoxy-4-hydroxystyryl ketone. The color change component is induced to change colors by addition of saliva and/or by a change in pH of the composition. The composition and methods provide benefits including providing visual cues to the user.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 61/293,079, filed on Jan. 7, 2010, which is incorporated herein byreference.

BACKGROUND

This application relates to oral care compositions, and moreparticularly to compositions comprising chalcone compounds.Specifically, the invention relates to oral care compositions containingphenyl-3-methoxy-4-hydroxystryryl ketone as a pH induced color changecomponent. Such compositions include for example, dentifrices.

The use of mouthwash is adjunctive to toothbrushing. However, the use ofmouthwash does not require as much active interaction as does brushingone's teeth. It also does not provide a signal that anything hashappened during the use aside from mouth feel that is usually astringentor burning.

SUMMARY

The present invention provides, in various embodiments, oral carecompositions comprising a chalcone color change component, in which thecomposition changes color by contact with saliva and/or by a change inpH. More specifically, the chalcone color change component isphenyl-3-methoxy-4-hydroxystyryl ketone (CHAK4). In one embodiment, theoral care composition is a mouthwash.

Yet another feature of the invention relates to a method of making anoral care composition comprising phenyl-3-methoxy-4-hydroxystyryl ketone(CHAK4) as a color change component.

Still another feature of the invention relates to a method of providingoral health benefits to an oral surface.

BRIEF DESCRIPTION OF THE FIGURE

FIG. 1 is a gray-scale depiction of a plate showing the effects ofsaliva on the color of CHAK4 containing mouthwashes.

DETAILED DESCRIPTION

The present invention provides compositions and methods foradministration to, or use with, a human or other animal subject.Preferably, specific materials and compositions to be used in thisinvention are, accordingly, pharmaceutically- orcosmetically-acceptable. As used herein, such a “pharmaceuticallyacceptable” or “cosmetically acceptable” component is one that issuitable for use with humans and/or animals to provide the desiredtherapeutic, sensory, decorative, or cosmetic benefit without undueadverse side effects (such as toxicity, astringent taste, irritation,and allergic response) commensurate with a reasonable benefit/riskratio. The following definitions and non-limiting guidelines should beconsidered in reading and interpreting the description of this inventionset forth herein.

All references cited herein are hereby incorporated by reference intheir entirety.

The description and specific examples, while indicating embodiments ofthe invention, are intended for purposes of illustration only and arenot intended to limit the scope of the invention. Recitation of multipleembodiments having stated features is not intended to exclude otherembodiments having additional features, or other embodimentsincorporating different combinations of the stated features. SpecificExamples are provided for illustrative purposes of how to make, use andpractice the compositions and methods of this invention and, unlessexplicitly stated to recite activities that have been done (i.e., usingthe past tense), are not intended to be a representation that givenembodiments of this invention have, or have not, been performed.

As used herein, the words “preferred” and “preferably” refer toembodiments of the invention that afford certain benefits, under certaincircumstances. However, other embodiments may also be preferred, underthe same or other circumstances. Furthermore, the recitation of one ormore preferred embodiments does not imply that other embodiments are notuseful, and is not intended to exclude other embodiments from the scopeof the invention. As used herein, the word “include,” and its variants,is intended to be non-limiting, such that recitation of items in a listis not to the exclusion of other like items that may also be useful inthe materials, compositions, devices, and methods of this invention. Ina similar manner, the description of certain advantages or disadvantagesof known materials and methods is not intended to limit the scope of theembodiments to their exclusion. Indeed, certain embodiments may includeone or more known materials or methods, without suffering from thedisadvantages discussed herein.

As used herein, the term “comprising” means that other steps and othercomponents that do not affect the end result may be utilized. The term“comprising” encompasses the expressions “consisting of,” and“consisting essentially of.” The expression “effective amount,” as usedherein denotes an amount of a compound or composition sufficient tosignificantly induce a positive benefit, preferably an oral healthbenefit, but low enough to avoid serious side effects, i.e., to providea reasonable benefit to risk ratio, within the sound judgment of aperson having ordinary skill in the art. The use of singular identifierssuch as “the,” “a,” or “an” is not intended to be limiting solely to theuse of a single component, but may include multiple components.

As referred to herein, an “oral care composition” is any compositionthat is suitable for administration or application to a human or animalsubject for enhancing the health, hygiene or appearance of the subject,including the prevention or treatment of any physiologic condition ordisorder, and providing sensory, decorative or cosmetic benefits andcombinations thereof. By “oral care composition” as used herein is meanta composition for which the intended use can include oral care, oralhygiene, or oral appearance, or for which the intended method of use cancomprise administration to the oral cavity.

The oral care compositions of the various embodiments preferably are inthe form of a dentifrice. The term “dentifrice” as used throughout thisdescription, denotes a paste, gel, or liquid formulation.

The expressions “carrier” or “aqueous carrier” as used throughout thisdescription denote any safe and effective materials for use herein. Suchmaterials include, for example, thickening agents, humectants, ionicactive ingredients, buffering agents, anticalculus agents, abrasivepolishing materials, peroxide sources, alkali metal bicarbonate salts,surfactants, titanium dioxide, coloring agents, flavor systems,sweetening agents, antimicrobial agents, herbal agents, desensitizingagents, stain reducing agents, and mixtures thereof.

All percentages and ratios used herein are by weight of the oral carecomposition, unless otherwise specified. All measurements are made at25° C., unless otherwise specified.

Chalcones are a family of naturally occurring compounds found in anumber of plant species. All chalcone compounds share a common aromaticketone core. Chalcones have been shown to have antibacterial,antifungal, antitumor and anti-inflammatory properties.

Chalcone derivatives for use in oral compositions are described inco-pending International Application Serial No. PCT/US2009/068688,entitled “Chalcones as Enhancer of Antimicrobial Agents,” AttorneyDocket No. 8899-00-OC, hereby incorporated by reference in its entirety.The chalcone derivatives described in this co-pending patent applicationare believed to have the properties of enhancing efficacy in in vitroscreening, when combined with various anti-infective agents usingbacteria, viruses and yeast. These compositions and compounds also wereefficacious when tested in vivo using mice and guinea pig modelsinfected with microorganisms.

One chalcone derivative described in this co-pending patent applicationis 3-(4′-Hydroxy-3′-methoxy-phenyl)-1-phenyl-prop-2-ene-1-one, alsoknown as phenyl-3-methoxy-4-hydroxystyryl ketone, and which will bereferred to herein as CHAK4. The formula for CHAK4 is as follows:

In studies with compositions including CHAK4, the present inventorsunexpectedly observed that the addition of the compositions to anysurface containing human saliva produced an immediate and distinctivecolor change. This surprising discovery that saliva causes a color shiftto a composition comprising CHAK4 led the present inventors to believethat pH had an effect on the color of a composition comprising CHAK4.

A solution with a pH of 3.8 comprising CHAK4 and no additional coloranthas a yellow color. As the pH of the solution increases towards neutral,the color shifts from the yellow at a pH of 3.8 to a goldenrod color ata pH of 4.8 to a red color at a pH of 6.8. The present inventors'research demonstrated that unique to CHAK4 is its ability to changecolor in response to small fluctuations in pH. This effect on pH on thecolor of a composition comprising CHAK4 may be used in oral carecompositions as a feedback signal.

In one embodiment, the present invention provides an oral carecomposition comprising CHAK4. The oral care composition may comprisefrom 0.01% to 10% CHAK4, or from 0.05 to 5%, or from 0.1% to 1%, or from0.1% to 0.5%. In one embodiment, the oral care composition comprisesfrom 0.01% to 0.05% CHAK4.

The pH of the oral care composition may be from 2.0 to 12.0. In variousembodiments, the pH of the oral care composition may be from 3.5 to 5.0.The normal pH of saliva is near neutral. Addition of saliva to an acidicsolution comprising CHAK4 would increase the pH level towards basic,thereby causing a color shift in the solution. The color change mayserve as a feedback signal to a user that the composition is working.

In another embodiment, colorant may be added to the oral compositioncomprising CHAK4. The additional colorants may be added to compositionshaving CHAK4 to provide a variety of starting color aesthetics. The samecolor shifting effect of CHAK4 is also observed in solutions comprisingadditional colorants.

In certain embodiments, the compositions of the present invention areoral care compositions, suitable for administration to the oral cavity.Such compositions include dentifrices, mouthwashes, dental gels,lozenges, beads, gums, oral strips, mints, liquid toothpastes, sprays,paint-on gels, lip balms, whitening strips, breath strips, oral chews,and combinations thereof. An oral care composition disclosed herein canbe used, for example, for cavity prevention, whitening, plaqueprevention or reduction, gingivitis prevention or reduction, tartarcontrol, sensitivity prevention or reduction, or breath malodorprevention or reduction, and stain prevention.

In a preferred embodiment, the oral composition is in the form of amouthwash. In a mouthwash preparation, the vehicle may comprise alcoholor may be alcohol free. In one embodiment, the vehicle is awater-alcohol mixture. Generally, the weight ratio of water to alcoholis in the range of from 1:1 to 20:1, preferably 3:1 to 10:1 and morepreferably 4:1 to 6:1. The total amount of water-alcohol mixture in thistype of preparation is typically in the range of from 70 to 99.9% byweight. The alcohol preferably is a non-toxic alcohol such as ethanol orisopropanol. Humectants such as glycerine and sorbitol may be present inamounts of 10-30% by weight. Liquid dentifrices typically contain 50-85%of water, may contain 0.5-20% by weight of non-toxic alcohol and mayalso contain 10-40% by weight of humectant such as glycerine and/orsorbitol. Reference to sorbitol refers to the material typicallyavailable commercially in 70% aqueous solutions. Ethanol is thepreferred non-toxic alcohol.

Organic surface-active agents also may be used in the compositions ofthe present invention to achieve increased prophylactic action, assistin achieving thorough and complete solvent dispersion of antiplaqueantibacterial agent throughout the oral cavity, and render the instantcompositions more cosmetically acceptable. The organic surface-activematerial is preferably anionic, nonionic or ampholytic in nature, and itis preferred to employ as the surface-active agent a detersive materialthat imparts to the composition detersive and foaming properties.Suitable examples of anionic surfactants are water-soluble salts ofhigher fatty acid monoglyceride monosulfates, such as the sodium salt ofthe monosulfated monoglyceride of hydrogenated coconut oil fatty acids,higher alkyl sulfates such as sodium lauryl sulfate, alkyl arylsulfonates such as sodium dodecyl benzene sulfonate, higher alkylsulfoacetates, higher fatty acid esters of 1,2-dihydroxy propanesulfonate, higher fatty acid esters of taurine and the substantiallysaturated higher aliphatic acyl amides of lower aliphatic aminocarboxylic acid compounds, such as those having 12 to 16 carbons in thefatty acid, alkyl or acyl radicals, and the like. Examples of suitabletaurines and amides are N-methyl-N-cococyl taurate, N-methyl-N-oleoyltaurate, N-methyl-N-palmitoyl-taurate, N-lauroyl sarcosinate, and thesodium, potassium, and ethanolamine salts of N-lauroyl, N-myristoyl, orN-palmitoyl sarcosine which should be substantially free from soap orsimilar higher fatty acid material. The taurine compounds particularlyassist solution. The use of the sarconsinate compounds in the oralcompositions of the present invention is particularly advantageous sincethese materials exhibit a prolonged and marked effect in the inhibitionof acid formation in the oral cavity due to carbohydrate breakdown inaddition to exerting some reduction in the solubility of tooth enamel inacid solutions. Examples of water-soluble nonionic surfactants arecondensation products of ethylene oxide with various reactivehydrogen-containing compounds reactive therewith having long hydrophobicchains (e.g. aliphatic chains of 12 to 20 carbon atoms), whichcondensation products (“ethoxamers”) contain hydrophilic polyoxyethylenemoieties, such as condensation products of poly(ethylene oxide) withfatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g.sorbitan monostearate) and polypropyleneoxide (e.g. Pluronic materials).Amphoteric or zwitterionic surfactants also may be used in the variousembodiments.

The mouthwash composition also may contain an anticaries effectiveamount of fluoride ion source sufficient to supply 25 ppm to 5,000 ppmof fluoride ions. The sources of fluoride ions, or fluorine-providingcomponents are well known in the art as anticaries agents. Thesecompounds may be slightly soluble in water or more preferably fullywater-soluble. They are characterized by an ability to release fluorideions in water and by substantial freedom from undesired reaction withother compounds of the oral preparation.

The amount of fluorine-providing compound is dependent to some extentupon the type of compound, its solubility, and the type of oralpreparation, but it must be a non-toxic amount, generally 0.0005% to3.0% in the preparation. In a mouthwash preparation, an amount of suchcompound which releases up to 5,000 ppm of F ion by weight of thepreparation is considered satisfactory. Any suitable effectiveanticaries minimum amount of such compound may be used, but it ispreferable to employ sufficient compound to release 100 to 2,000 ppm,more preferably 300 to 1,500 ppm of fluoride ion.

Any suitable flavoring or sweetening material may also be employed.Examples of suitable flavoring constituents are flavoring oils, e.g. oilof spearmint, pepperment, wintergreen, sassafras, clove, sage,eucalyptus, marjoram, cinnamon, lemon, and orange, and methylsalicylate. Suitable sweetening agents include sucrose, lactose,maltose, xylitol, sodium cyclamate, perillatrine, AMP (aspartyl phenylalanins, methyl ester), saccharine and the like. Suitably, flavor andsweetening agents may each or together comprise from 0.001% to 5% ormore of the preparation, each being typically 0.1-2.5%.

Various other materials may be incorporated in the oral preparations ofthis invention such as whitening agents, preservatives, silicones,chlorophyll compounds and/or ammoniated material such as urea,diammonium phosphate, and mixtures thereof. These adjuvants, wherepresent, are incorporated in the preparations in amounts which do notsubstantially adversely affect the properties and characteristicsdesired. Significant amounts of zinc, magnesium and other metal saltsand materials, generally soluble, which would complex with activecomponents of the instant invention are to be avoided.

It will be understood that, as is conventional, the oral preparationsare to be sold or otherwise distributed in suitably labelled packages.Thus a container of mouthwash will have a label describing it, insubstance, as a mouthrinse or mouthwash and having directions for itsuse; and a liquid toothpaste will usually be in a collapsible or driptube, typically aluminum, lined lead or plastic, or other dispenser formetering out the contents, having a label describing it, in substance,as a liquid toothpaste or dentifrice.

In various embodiments, the present invention provides methods foradministering a functional material to a human or animal subject in needthereof, comprising topically applying to said subject a compositioncomprising CHAK4. As referred to herein, “administering” refers to anymethod by which a composition is applied on or administered to thesubject. In various embodiments, the administration is topical, whereinthe composition is applied to an external surface of the subject, suchas to a surface of the oral cavity (e.g., teeth, gingival, and tongue).The specific route and method of administration will depend, of course,on the intended use of the composition.

In various embodiments, the present invention provides methods for thetreatment of an oral care condition. As referred to herein, an “oralcare condition” is any disorder or condition which can be prevented ortreated by administration of a composition to the oral cavity, includingdisorders or conditions of the teeth, oral mucosa, gingiva and tongue.Such conditions include caries, gingivitis, periodontitis, and cosmeticconditions such as yellowing and malodour.

The embodiments described herein can be further understood by referenceto the following non-limiting examples.

EXAMPLES Example 1

CHAK4 was added to a starting base mouthwash formulation containingcetylpyridinum chloride that was colorless. CHAK4 added to the colorlessmouthwash changed the mouthwash formulation to a yellow color. Varyingconcentrations of CHAK-4 were used, from 0.01%, 0.05%, 0.1% and 0.5% byweight. The color of the mouthwash formulation for the 0.05 wt % CHAK-4produced the strongest color change, to an almost orange-like color. Theremaining formulations were bright yellow.

Example 2

This example illustrates the effect of saliva on the color of amouthwash solution comprising CHAK4. Mouthwash solutions were made inaccordance with the present invention with increasing concentrations ofCHAK4. 100 μl of mouthwash was added to wells on a 96 well plate.Increasing volumes of sterilized human saliva were then added to eachwell containing mouthwash.

As shown in FIG. 1, a systematic mixing of mouthwashes containingincreasing concentrations of CHAK4 with sterilized human saliva invarying concentrations demonstrated the sensitivity of the color changein the mouthwash to relatively small amounts of saliva. A distinctivecolor change is observed with the addition of saliva to the mouthwash.For each of the CHAK-4 formulations, (0.01%, 0.05%, 0.1%, and 0.5% byweight), the color change became more and more pronounced with moresaliva. In other words, starting at a relatively slight yellow color at1 μl saliva, as saliva concentration increased, the color changed fromyellow to more orange, with the exception of the 0.01%, in which thecolor became more distinctly yellow.

In the last two columns of the plate in FIG. 1 (F & G), neat activedissolved in 95% ethanol was combined with either saliva or sterilewater. Mixed with sterile water, CHAK4 retains its distinctive yellowcolor (G). However, when mixed with saliva, there is a clear change toan orange color (F), and again for each sample, the color became moreintense as the volume of saliva was increased.

Example 3

This example illustrates the effect of pH on the color of a mouthwashsolution comprising 0.1% CHAK4. CHAK4 was mixed into clear mouthwashsolutions and the pH adjusted. The solution was yellow at a pH of 3.8,goldenrod at a pH of 4.5, and red at a pH of 6.8. Within a relativelynarrow range of pHs, it was possible to induce a color change in fullmouthwash formulations containing 0.1% CHAK4.

Example 4

A typical mouthwash formulation as well as a formulation containingCHAK4 is provided in table 1. Each mouthwash formulation contained ablue dye, such that a mouthwash without CHAK4 was blue and the mouthwashformulations containing CHAK4 was green. The final formula color may betailored depending upon the type of colorant combined with the CHAK4.

TABLE 1 Ingredient Standard Formula Formula A Formula B Water BalanceBalance Balance Pluronic F127 0.25% 0.25% 0.25% Sorbitol 5.5% 0.0% 0.0%Propylene Blycol 5.0% 6.0% 6.0% Glycerin 7.5% 19.0% 19.0% Ethyl Alcohol6.0% 6.0% 6.0% Sweetener 0.001% 0.001% 0.001% Cetylpyridinium 0.055%0.055% 0.055% Chloride CHAK4 0.0% 0.01% 0.05% Sodium chloride 0.0% 0.0%0.03% Flavor 0.1% 0.1% 0.1%

Example 5

An in vitro study indicated that the color change in mouthwashcompositions including CHAK4 can be readily induced by mixing with smallamounts of saliva comparable to the amount that would be present whenrinsing in actual use.

Simulated mouthrinsing was conducted by combining a 15 mL mouthwash dosewith 1 mL of human saliva. Each mouthwash had a different startingcolor, and each displayed a perceivable color change after combiningwith saliva. This simulated rinsing study demonstrated that the additionof CHAK4 can yield a color change when combined with saliva in an actualusage situation. This example demonstrates the ease in which thestarting aesthetic can be adjusted, while still providing a verydiscernable and perceivable end color.

The examples and other embodiments described herein are exemplary andnot intended to be limiting in describing the full scope of compositionsand methods of this invention. Equivalent changes, modifications andvariations of specific embodiments, materials, compositions and methodsmay be made within the scope of the present invention, withsubstantially similar results.

1. An oral care composition comprising a chalcone color change componentthat is able to change color by addition of saliva and/or by a change inpH of the composition.
 2. The oral care composition of claim 1, whereinthe color change component comprises phenyl-3-methoxy-4-hydroxystyrylketone (CHAK4).
 3. The oral care composition of claim 1, wherein theoral care composition is a mouthwash.
 4. The oral care composition ofclaim 2, wherein the CHAK4 is present in an amount from 0.01% to 10% byweight of the composition.
 5. The oral care composition of claim 4,wherein the CHAK4 is present in an amount from 0.01% to 0.05%.
 6. Theoral care composition of claim 1, wherein the pH of the composition isin the range of from 2 to
 12. 7. The oral care composition of claim 6,wherein the pH of the composition is in the range of from 3.5 to
 5. 8. Amouthwash comprising a phenyl-3-methoxy-4-hydroxystyryl ketone in anamount from 0.01% to 10% by weight of the mouthwash.
 9. A method ofmaking an oral care composition comprising a color change componentcomprising adding phenyl-3-methoxy-4-hydroxystyryl ketone (CHAK4) to anorally acceptable carrier.
 10. The method of claim 9, wherein the CHAK4is added in an amount from 0.01% to 10% by weight of the composition.11. The method of claim 9, further comprising adjusting the pH to bewithin the range of from 3.5 to 5.0.
 12. A method of providing oralhealth benefits to an oral surface comprising contacting the oralsurface according to claim 1 with the oral care composition.